title: Studies in experimental autoimmune encephalomyelitis do not support developmental bisphenol a exposure as an environmental factor in increasing multiple sclerosis risk.
abstract: Multiple sclerosis (MS), a demyelinating immune-mediated central nervous system disease characterized by increasing female penetrance, is the leading cause of disability in young adults in the developed world. Epidemiological data strongly implicate an environmental factor, acting at the population level during gestation, in the increasing incidence of female MS observed over the last 50 years, yet the identity of this factor remains unknown. Gestational exposure to bisphenol A (BPA), an endocrine disruptor used in the manufacture of polycarbonate plastics since the 1950s, has been reported to alter a variety of physiological processes in adulthood. BPA has estrogenic activity, and we hypothesized that increased gestational exposure to environmental BPA may therefore contribute to the increasing female MS risk. To test this hypothesis, we utilized two different mouse models of MS, experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice (chronic progressive) and in SJL/J mice (relapsing-remitting). Dams were exposed to physiologically relevant levels of BPA in drinking water starting 2 weeks prior to mating and continuing until weaning of offspring. EAE was induced in adult offspring. No significant changes in EAE incidence, progression, or severity were observed with BPA exposure, despite changes in cytokine production by autoreactive T cells. However, endocrine disruption was evidenced by changes in testes development, and transcriptomic profiling revealed that BPA exposure altered the expression of several genes important for testes development, including Pdgfa, which was downregulated. Overall, our results do not support gestational BPA exposure as a significant contributor to the increasing female MS risk.
authors.affiliation: Department of Medicine, Immunobiology Program, University of Vermont, Burlington, Vermont 05405, USA.
authors.forename: Dimitry N
authors.initials: DN
authors.lastname: Krementsov
authors.forename: Anne
authors.initials: A
authors.lastname: Katchy
authors.forename: Laure K
authors.initials: LK
authors.lastname: Case
authors.forename: Frances E
authors.initials: FE
authors.lastname: Carr
authors.forename: Barbara
authors.initials: B
authors.lastname: Davis
authors.forename: Cecilia
authors.initials: C
authors.lastname: Williams
authors.forename: Cory
authors.initials: C
authors.lastname: Teuscher
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced*; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000139:chemically induced*; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D012306:Risk; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D007371:Interferon-gamma; D020381:Interleukin-17; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; PDGF.; T cell; autoimmunity; central nervous system; developmental; endocrine disruption; environmental exposure; experimental autoimmune encephalomyelitis; gestational; multiple sclerosis; testes